The invention is directed to a process for the production of pyridines substituted in the 2- and 6-positions by an aromatic or heteroaromatic group. These substituted pyridines are important intermediate products for the production of medicines, plant protective agents and synthetic resins.
It is known that 2,6-diphenyl pyridine is formed when diphenyl pyridone dicarboxylic acid ester is distilled in the presence of zinc dust. The ester is recovered by dehydrogenation of the diphenyl piperidone dicarboxylic acid ester formed in the reaction of acetone dicarboxylic acid ester with benzaldehyde and ammonia (Berichte Vol. 42 (1910) pages 2020-2025). It is also known to start from acetophenone in production of the 2,6-diphenyl pyridine. For this purpose acetophenone is condensed with phenyl propargyl aldehyde to 1,5-diphenylpentin-(1)-en-(3)-one-(5), this reacted with perchloric acid to form 2,6-diphenyl pyrylium perchlorate and this finally converted by means of ammonia into the 2,6-diphenyl pyridine (Berichte Vol. 93 (1960) pages 1253-1256). There is also obtained 2,6-diphenyl pyridine from acetophenone and N,N,N-trimethyl-hydrazonium tetrafluoroborate or in a corresponding manner from 4-methyl acetophenone there is formed 2,6-diphenyl-3,5-dimethyl pyridine or from propiophenone there is formed 2,6-di-p-tolyl pyridine (J. Amer. Chem. Soc. Vol. 88 (1966) pages 3654-3655). It is further known to recover 2,6-diphenyl pyridine and various substituted 2,6-diphenyl pyridine by dehydrogenation of the corresponding piperidines by means of sulfur. The piperidines are produced by reduction of the corresponding 4-piperidone (J. Indian Chem. Soc. Vol. 32 (1955) pages 274-278).
Besides it is known that 2,6-bis(2'-pyridyl)-pyridine can be recovered by decarboxylation of 2,6-bis (2'-pyridyl)-pyridine-3,5-dicarboxylic acid. The carboxylic acid is accessible in several steps from 2,6-bis(2'-pyridyl)-3,5-di-carbethoxy-1,4-dihydropyridine resulting from the reaction of ethyl picolinoyl acetate with formaldehyde (J. Org. Chem. Vol. 26 (1961) pages 4415-4418).
Furthermore, it is known that 2,6-bis(2'-pyridyl)-pyridine is formed as a byproduct besides 2-(2'-pyridyl)-pyridine in the reaction of pyridine with potassium peroxydisulfate (East German Patent No. 23,118) or with pyridine-N-oxide in the presence of Pd-Pt-catalysts (Yakugaku Zasshi Vol. 93 (1973) pages 144-148). Also in the heating of pyridine in the presence of Raney nickel there is formed as byproduct 2,6-bis(2'-pyridyl)-pyridine and in the same manner there is formed in the heating of substituted pyridines the corresponding substituted compounds (J. Chem. Soc. (1956) pages 616-620). 2,6-Bis(3-pyridyl)-pyridine is produced when 3-acetyl pyridine is reacted with dimethylamine hydrochloride and formaldehyde to form an aminoketone and this aminoketone is further reacted with 3-pyridinium acetyl pyridine bromide obtained from 3-acetyl pyridine by way of 3-bromoacetyl pyridine (Synthesis (1976) pages 1-24).
Finally, it is known to produce 2,6-bis(2'-thienyl)-pyridine by reaction of 2,6-dichloropyridine with 2-lithiothiophene (Angew. Chem. Vol. 83 (1971) pages 796-799).
The known processes are little suited for use on an industrial scale. They are expensive and cumbersome to handle or give the desired compounds only in low yield or as byproducts. Besides in several cases the necessary starting materials are only accessible with difficulty.